Why IVF and ICSI success rates vary for struggling couples

IVF and ICSI dominate infertility care—but success remains unpredictable

Infertility care is now heavily structured around assisted reproduction technology (ART). IVF and its close relatives have become the default pathway, largely because they give clinicians control over the part of reproduction that can be influenced reliably, such as fertilisation and early embryo development.

But even in this highly optimised setting, outcomes still vary widely from one couple to the next. According to the European Society of Human Reproduction and Embryology (ESHRE), in 2020, the mean pregnancy rate per embryo transfer was about 33% after IVF and intracytoplasmic sperm injection (ICSI), about 36% after frozen embryo transfer, and around 51% after egg donation, with a success rate higher in younger patients.

IVF works often enough to have become the backbone of treatment, but it still leaves a lot of biology unaddressed. Implantation is a clear example. Successful implantation depends on a dialogue between embryo and endometrium, and when that dialogue fails, the embryo simply doesn't take, in many cases without a clear explanation.

Reviews of recurrent implantation failure describe it as a persistent clinical phenomenon, affecting an estimated 10% of couples undergoing IVF and embryo transfer. If you can improve endometrial receptivity, reduce inflammation, or shift the local environment in a measurable way, you could theoretically raise the odds of success without changing the IVF process itself. Another blind spot is that assisted reproduction often works around underlying biology rather than correcting it, especially in cases of male factor infertility. Technologies such as ICSI can bypass many sperm-related barriers by design, but it's not a direct treatment of the male reproductive problem itself.

Over time, ICSI also expanded well beyond clear male-factor indications in many settings, and there has been criticism that it is used where it doesn't improve outcomes and may add cost and complexity. A 2025 analysis in Reproductive BioMedicine Online argues that ICSI should be limited to couples with male infertility, describing widespread overuse in ART.

This is also where the female-centred dynamic of infertility care becomes hard to ignore. Even when infertility originates in the male partner, the most established solutions tend to move the clinical burden toward the female body: ovarian stimulation, egg retrieval, embryo transfer, and hormonal support. That's not because clinics ignore male factors, but because the dominant toolbox is procedural and couples-focused, and the interventions that reliably change outcomes have historically been built around the female cycle and the IVF workflow.

"Although infertility is 50% men related, there is no approved treatment addressing this segment. There is no standard of care for half the population." - Florent Ferré, CEO of Igyxos

"The issue that we are facing with IVF is that more and more women don't respond well to the hormonal stimulation, which is the first part of the IVF treatment, and therefore are not very successful when they go through the procedure. This is why there is a need for more effective treatment," said Florent Ferré, CEO of Igyxos, a fertility-focused biotech based in France. Much of the current innovation isn't trying to replace IVF or promise cures. It's trying to intervene in the unresolved steps where IVF has blind spots.

Improving IVF Odds Without Replacing It

Fertilisation and early embryo development can be managed and optimised in the lab, but whether an embryo actually establishes a pregnancy still depends on biological parameters: endometrial receptivity, immune signalling, uterine contractility, and early placentation. If you can make the uterus more receptive at the moment of implantation, you might raise success rates without changing the IVF process itself.

Oxolife is currently working on that segment. The Barcelona-based company is developing OXO-001, a non-hormonal oral drug that acts on the endometrium to enhance implantation during IVF and ICSI cycles. "Unlike current IVF workflows, which focus primarily on selecting the best embryos, OXO-001 acts directly on the endometrium. It modulates the expression of proteins involved in adhesion, invasion, and the completion of embryo implantation, improving the uterine environment rather than compensating for its limitations," explained the company's CEO, Agnès Arbat.

OXO-001 is an adjunct therapy aimed at increasing the probability that an embryo transfer results in a pregnancy and, ultimately, a live birth. In phase 2, Oxolife reported an ongoing pregnancy rate at 10 weeks of 46.3% versus 35.7% in the placebo group, and a live birth rate of 42.6% versus 35.7%.

But with implantation adjuncts, early signals don't always survive scale-up. "Implantation is an exceptionally complex biological process, and experiences such as ObsEva's have shown how difficult it is to demonstrate a clinical benefit on ultimate endpoints like ongoing pregnancy or live birth, endpoints that are long, variable, and unforgiving."

Treating the Fertility Environment

For a large subset of patients, infertility is a chronic state, and endometriosis is the clearest example of that category. Endometriosis affects roughly one in ten women of reproductive age, and it is strongly associated with infertility. The clinical effect is that many patients are funnelled into ART, not because IVF is the ideal treatment, but because it is the most reliable workaround once the underlying condition has already altered reproductive potential.

Indeed, a recent study led on more than four million women over 30 in the U.K. suggests that women suffering from infertility issues are twice as likely to be diagnosed with endometriosis. However, the same study suggests that endometriosis patients had 4 times more chances of pregnancy compared to women with infertility due to other factors. The study also specified that this was particularly true when the disease was diagnosed early.

While endometriosis is common, it is often diagnosed late, and delays can stretch for years, up to a decade, before patients receive a diagnosis. A delayed diagnosis logically compresses the reproductive timeline.

This diagnostic delay is where new approaches to fertility are beginning to emerge. One example is Viramal, a company focused on women's health conditions that sit upstream of fertility outcomes, including endometriosis. Rather than positioning itself as an IVF outcomes company, Viramal targets the tissue environment that makes conception harder in the first place, particularly when the disease is diagnosed late.

Viramal's lead program, VML-0501, is being tested in phase 2b as a locally delivered treatment for endometriosis. The treatment acts directly on the pelvic tissue, and while pregnancy isn't the primary endpoint, the company argues that addressing the inflammatory environment has consequences on fertility.

The Elephant in the Room: Funding

IVF has made the infertility burden more manageable, but it has also shaped the field around what clinics can control procedurally while leaving the hardest biology to variability and repeated cycles.

The investment story sits awkwardly on top of that, largely because fertility occupies an uncomfortable category in healthcare financing. Clinically, infertility is a couple's condition, with male biology contributing materially to outcomes. Financially, however, it is still often bundled into women's health, with all the market-sizing shortcuts that label can trigger.

Women's health is frequently described as underfunded; only 1% of healthcare research and innovation goes to female-specific conditions beyond oncology. "Women's health" is often treated as a narrow vertical, frequently reduced to reproductive care. Yet women's health outcomes extend far beyond reproduction and reproduction itself is not a women-only issue.

The companies emerging now are not replacing IVF so much as trying to make parts of reproduction less of a black box. This new wave of companies will live or die on unforgiving endpoints, but also on whether the field can be framed as a mainstream medical need rather than a niche category. As Florent Ferré put it, borrowing a characteristically French expression, "Il faut remettre l'église au milieu du village," literally, to put the church back at the center of the village. In other words, there are still quite a lot of misconceptions around fertility, and the record needs to be set straight in order for the field to accelerate.